Epstein-Barr virus and human papillomavirus infections and clinicopathological characteristics in oral squamous cell carcinoma in Guangzhou: a study based on specimens from affiliated hospitals of Sun Yat-sen University

Objective To investigate the infection status and clinicopathological characteristics of Epstein-Barr virus（EBV）and human papillomavirus（HPV）in oral squamous cell carcinoma（OSCC）in Guangzhou，China. Methods A total of 304 OSCC specimens were collected from Guangzhou，including 123 cases from the Third Affiliated Hospital of Sun Yat-sen University（January 2014 to December 2024）and 181 cases from Sun Yat-sen Memorial Hospital of Sun Yat-sen University（January 2017 to December 2018）. Polymerase Chain Reaction（PCR）was used to detect viral DNA，in situ hybridization was used to assess EBV-encoded RNAs（EBER），and immunohistochemistry was performed to identify viral-related proteins and determine the type of infection. Results Among the 304 OSCC specimens，26.3%（80/304）were EBV-PCR positive，with 63.8%（51/80）diagnosed at TNM stage I/II. Compared with EBV-negative cases，the difference in tumor staging was statistically significant（<i>P = </i>0.042）. Among the EBV-PCR-positive OSCC cases，the EBER-positive rate was 33.8%（27/80），with 92.6%（25/27）localized in the cytoplasm. The detection rates of EBV-encoded nuclear antigen-1（EBNA-1），latent membrane protein-1（LMP-1），and EBV-encoded nuclear antigen-2（EBNA-2）were 83.8%（67/80），81.3%（65/80），and 56.3%（45/80），respectively，while the lytic protein ZEBRA was not detected. Type III latent infection accounted for 41.3%（33/80）. In contrast，HPV DNA was detected in only 2.6%（8/304）of OSCC cases，among which two were p16-IHC positive. Only one case of OSCC showed EBV-HPV coinfection. Conclusions Based on samples collected from Sun Yat-sen University affiliated hospitals，EBV infection is relatively prevalent in OSCC cases in Guangzhou，mainly characterized by type III latency and cytoplasmic localization of EBER，suggesting a potential role of EBV in the pathogenesis of OSCC. In contrast，HPV-related OSCC appears to be rare and likely plays a limited pathogenic role.